Process for preparing same



Patented June 27, 1950 UNITED STATES- AMINOALKYIESULFONYL PIPERAZINES AND PROCESS FOR PREPARING SAME Robert Michel Jacob, Ablon-sur-Seinc, and Edouard Suau, Choisy-le-Roi, France, assignors to Societe des Usines Chimiques RhonvPonlenc, Paris, France, a French body corporate No Drawing. Application June 17, 1949, Serial No. 99,867. In France June 29, 1948 Where R has the significance given above, with a compound of the general Formula III:

where n has the significance given above.

According to yet a further feature of the inven- III tion compounds of general Formula I are pro-.

duced by condensing sulphonyl chloride of the general Formula IV:

where R has the significance given above, with a compound of the general formula:

Where n has the significance given above.

The aminoalkyl sulphonyl piperazines thus obtained have valuable physiological properties and are particularly eifective in treating states of traumatic or haemorrhagic shock.

The following examples will serve to illustrate 11 Claims. (Cl. 260268) the invention but are not to be regarded as limiting the invention in any way. Melting points were determined by the capillary method except Where otherwise stated. f

Example I A mixture a 59.2 g. of N-bis-(B-chlorethYD- p-toluenesulp'honamide, M. P. 47 C., and 92 g. of

- N.N-diethylethylene diamine is heated under reflux for 1 hour.. After cooling the mixture is-dissolved in 300 cc. of waterand-lef-t to crystallise in .the cold state, The crystalline product separated by centrifuging and is-Washed in water, and then dried in vacuo in a desiccator in thepresence of potash in pellet form. 63 g. of l-p-toluenesulphonyl 4 B diethylaminoethyl piperazine, MP. -5l C. are obtained. Its di-hydrochloride, after recrystallisation from alcohol, melts at 2l0-21l C. (on the Maquenne block) Example II By proceedingas in'Example I but using 5, g. of N-bis- (s-chlorethyl) -benzene sulphonamide M. P. 47-48? C., and 8.7 g. of N.N-diethyl-.1 :3- propylene diamine, l-benzenesulphonyl4-'y-diethylaminopr'opyl-piperazine is obtained. iThiS substance, after recrystallisation from-cyclohexane, melts at HE-79 C.

Example I I I An ethereal solution of 14.5.g'. of 1-'y+diethy1- amino-propyl-piperazine is poured. drop-by-Tdrop into an ethereal solution of .93 g;- of: ethane sulphonyl chloride, with agitation and cooling. A pasty precipitate isformed, which turns slightly yellow. It is left for sometime at room tempera.- ture, and then dissolved in water. Dilute sulphuric acid'is added until the solution is'just acid to Congo red. The acid solution is decanted and the residue is made alkaline with an excess of caustic soda (36 B.) and then extracted with ether. On evaporation of the ether from the'extract obtained an oil is obtained which is rectified under reduced pressure. 13.7 g. of l-ethanesulphonyl-4-'y-diethy1aminopropyl piperazine, which distils at 189-190" C. under a pressure of 1.5 mm. of mercury, is thus recovered. The corresponding picrate melts at 230-231 C. (on the Maquenne block).

The initial l-v-die'thylaminopropyl piperazine may be obtained in good yield and in very pure condition by acid hydrolysis of the l-benzenesulphonyll-' -diethylaminopropyl-piperazine referred to in Example II. This base distils at about C. under a pressure of 27 mm. of mercury and its picrate melts at 240 C. (on the Maquenne block).

Example IV By proceeding as described in Example III, but

with 10.5 g. of l-p-diethylaminoethyl piperazine and 7.3 g. of ethanesulphonyl chloride, 12.3 g. of

1 ethanesulphonyl 4 ,8 diethylaminoethylpiperazine are obtained. This substance distils at 158-159" C., under a pressure of 95 mm. of mercury and its picrate melts at 218-219 C. (on the Maquenne block). 7 v

The initial l-p-diethylaminoethyl piperazine is readily obtained by acid hydrolysis of the l-ptoluenesulphonyll-fi-diethylaminoethyl piperazine referred to in Example, I. This base distils at 131-132 C. under a pressure of 26 mm. of mercury and its picrate melts at 233 C. (on the Maquenne block).

Example V By proceeding as in Example III, but with 13.3 g. of l-"y-diethylaminopropyl' piperazine and 7.6 g. of methane-sulphonyl chloride, 13.5 g. of 1- methanesulphonyl-4-y-diethylamino propyl piperazine, which distils at 164-165" C. under a pressure of 0.9 mm. of mercury, is obtained.

Example VI By'proceeding as described in Example III,

but with 10.5 g. of l-fl-diethylaminoethyl piperazine and 6.5 g. of methanesulphonyl chloride, 12.7 g. of l-methanesulphonyl--fi-diethylamlno- Aminoalkyl sulphonyl piperazines of the general formula:

R-sm-rt N (CH),.N(O,H5)2

where n is selected from 2 and 3 and R is selected 3 from the class consisting of lower alkyl radicals,

the benzene radical and lower-alkyl-substituted benzene radicals.

2. Aminoalkyl sulphonyl piperazines of the general formula:

CHr-SOr-l N- omyr-molmjg where n is selected from 2 and 3.

. 3. Aminoalkyl sulphonyl piperazines of th general formula:

where n is selected from 2 and 3.

-4.Aminoalkyl sulphonyl piperazines of the general formula:

where n is selected from 2 and 3.

' I where n is selected from 2 and 3 and R is selected 5. l-p-toluenesulphonyl-i-p-diethylaminoethyl piperazine;

6. 1-ethanesulphonyl-4 fl diethylaminoethyl piperazine.

q 7. l-methanesulphonyl-vi-pdiethylaminoethyl piperazine.

8. l-ethanesulphonyll-vdiethylaminopropyl piperazine. I

9. 1-methanesulphonyl-4-v diethylaminopro- 'pyl piperazine:

10. Process for the production of aminoalkyl sulphonyl piperazines of the general formula:

from the class consisting of lower alkyl radicals,

the benzene radical and lower-alkyl-substituted benzene radicals which comprises condensing a sulphonyl chloride of the general formula:

where R has thesignificance given above, with a compound of the general formula:

where R has the significance given above, with a compound of the general formula:v

where n has the significance given above, the said condensation and separation of the product being effected by mixing the reactants together in ethereal so1ution,- dissolving the product in water, making the resulting solution acid, extracting the residue with ether, evaporating the ether from the extract and distilling the residue under reduced pressure.

ROBERT MICHEL JACOB.

EDOUARD SUAU.

No references cited. 

1. AMINOALKYL SULPHONYL PIPERAZINES OF THE GENERAL FORMULA: 